Use Of Oxandrolone In The Treatment Of Burns And Other Wounds

ABSTRACT

The subject invention provides a method of treating burn-induced weight loss in a burn patient which comprises administering a therapeutically effective amount of an oxandrolone to the patient. The invention also provides a method of treating a wound in a patient suffering from a wound which comprises administering a therapeutically effective amount of an oxandrolone to the patient. The subject invention further provides a method of treating burn-induced weight loss in a burn patient which comprises administering a therapeutically effective amount of an oxandrolone in conjunction with a protein supplement to the patient.

This application claims priority of U.S. Provisional Application Ser.No. 60/032,414, filed Dec. 5, 1996, the contents of which are herebyincorporated into this application by reference.

Throughout this specification, various publications are referenced byArabic numerals within parentheses. Full citations for these referencesmay be found at the end of the specification immediately preceding theclaims. The disclosure of these publications in their entireties arehereby incorporated by reference into this specification in order tomore fully describe the state of the art to which this inventionpertains.

BACKGROUND OF THE INVENTION

Burns

Over one million people are involved in burn accidents in the UnitedStates each year. Approximately 150,000 of these patients arehospitalized and over 6000 of these die each year (1).

Following thermal injury, severe protein and fat wasting occurs (1).Loss of as much as 20% of body protein may occur in the first two weeksfollowing major burn injury (2). Increased oxygen consumption, metabolicrate, urinary nitrogen excretion, fat breakdown and steady erosion ofbody mass are all directly related to burn size and return to normal asthe burn wound heals or is covered (1). The metabolic rate in patientswith burns covering more than 40% of total body surface is twice as highas the metabolic rate in people without burns (1).

Although the danger associated with acute burn-induced weight loss,especially lean body mass has well been defined, the impact of thisprocess on patient outcome continues to be severely underestimated. Thefocus of management of critical illness post-burn remains that ofcardiopulmonary support and infection control while stress inducedcatabolism may proceed unchecked leading to a rapid loss of lean tissue(fat-free), mainly muscle which is followed by protein loss indiaphragm, heart, then liver, kidney and splanchnic bed. The loss ofvisceral proteins may actually begin very early after injury and themuscle protein is used to replace organ losses. It is clear that theresponse to severe injury or post-surgical infection will becomeauto-destructive if not contained. Complications will occur includingmultiple organ dysfunction, the leading cause of death in the post-burnperiod. A loss of lean body mass exceeding 40% of total is usuallyfatal. This muscle loss corresponds to a comparable loss of total bodyprotein which affects all organ functions.

Although major advances in surgical nutrition have also been made,attempt at controlling the protein loss often come too little and toolate to prevent the catabolism induced complications. The degree of leantissue loss corresponds very precisely with not only profound weakness,including chest wall and diaphragm impairment, but also decreased immunefunction, leading to infection, usually pneumonia.

Both lymphocyte and neutrophil immune defenses are impaired. Loss ofmyocardial muscle leads to decreased contractility. Wound healingbecomes markedly impaired and an open wound soon becomes an infectedwound. Cell metabolic abnormalities occur including decreased cellenergy charge and impaired calcium kinetics.

Despite this well defined concept, a routine assessment of body weightand body protein loss and an aggressive attempt at preventing earlyprotein depletion by controlling the host response to injury andoptimizing anabolism is not performed.

The current therapy of burn injury, namely high protein nutrition andearly wound closure attenuates the process but patients with large burnsenter the recovery phase with a significant deficit in muscle mass.Since the peak rate of restoration of muscle mass, using endogenousstimuli alone, including good nutrition approximates 1 to 1.5 pounds aweek, restoration of lean body mass usually requires months.

Use of the anabolic agent, human growth hormone, can increase anabolicactivity in the burns, but high expense and complications such ashyperglycemia have prevented widespread use of this agent (3). Thisagent also has to be administered by injection.

Since the rate of recovery of lean body mass dictates disability time,an increased rate would be of tremendous functional and economic valuein burn patients.

The subject invention provides therapies that increase the rate ofrecovery of lean body mass, thereby reducing the length of stay in ahospital and reducing rehabilitation time. Moreover, the subjectinvention provides therapies that increase the rate of wound healing.This is of great importance in burn-patients, especially in thosepatients that receive skin grafts. This is also important inburn-patients which have wounds at donor sites.

Oxandrolone

Oxandrolone (17-methyl-17-hydroxy-2-oxa-5-androstan-3-one) is a knowncompound which is commercially available. The preparation of oxandroloneis described, inter alia, in U.S. Pat. No. 3,128,283. Oxandrolone is ananabolic steroid synthetically derived from testosterone. Oxandrolonehas a unique chemical structure compared with other testosteroneanalogs. Oxandrolone contains an oxygen rather than a carbon atom at the2-position within the phenanthrene nucleus (4) and lacks a 4-enefunction in the A-ring. The anabolic activity of oxandrolone isapproximately 6 times greater than its androgenic activity and has beenfound to be 6.3 times greater than that of methyltestosterone (4).

Anabolic activity refers to the ability to cause nitrogen retention,promoting weight gain and increasing muscle strength. Androgenicactivity refers to the ability to enhance male characteristics (i.e.secondary sex characteristics such as facial hairs and voice changes).Because of the high ratio of anabolic to androgenic activity,oxandrolone is less likely to cause adverse cosmetic consequences inwomen than many testosterone analogs.

Furthermore, in contrast to the majority of oral androgenic anabolicsteroids (e.g. micronized testosterone, methyltestosterone,fluoxymesterone), oxandrolone undergoes relatively little hepaticmetabolism (5, 6).

Oxandrolone has been administered to malnourished patients withalcoholic hepatitis (7, 8). Oxandrolone has been shown to be safe evenin dosages of up to 80 mg/day in patients with alcoholic hepatitis (7).

The subject invention discloses the use of an oxandrolone for thetreatment of cachexia, muscle wasting and involuntary weight lossassociated with wounds, especially burns.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1: Effect of oxandrolone and increased protein content on therecovery phase in burn patients (Example 1): measurements of energylevel, therapy index and weight gain of burn patients in Groups 1, 2 and3.

FIG. 2: Body weight of patients (Example 1) with burn injury in Group 1.

FIG. 3: Body weight of patients (Example 1) with burn injury in Group 2.

FIG. 4: Body weight of patients (Example 1) with burn injury in Group 3.

FIG. 5: Energy level (0-10) of burn patients (Example 1) in Groups 1, 2and 3.

FIG. 6: Therapy index (0-10) of burn patients (Example 1) in Groups 1, 2and 3.

FIG. 7: Effect of oxandrolone and increased protein content on therecovery phase in burn patients (Example 2): measurements of weight gainin Groups 1, 2 and 3.

FIG. 8: Body weight of patients (Example 2) with burn injury in Groups1, 2 and 3.

FIG. 9: Therapy index (0-10) of burn patients (Example 2) in Groups 1, 2and 3.

SUMMARY OF THE INVENTION

The invention also provides a method of treating a wound in a patientsuffering from a wound which comprises administering a therapeuticallyeffective amount of an oxandrolone to the patient.

The subject invention provides a method of treating burn-induced weightloss in a burn patient which comprises administering a therapeuticallyeffective amount of an oxandrolone to the patient.

The subject invention further provides a method of treating burn-inducedweight loss in a burn patient which comprises administering atherapeutically effective amount of an oxandrolone in conjunction with aprotein supplement to the patient.

DETAILED DESCRIPTION OF THE INVENTION

Oxandrolone as used herein encompasses17-methyl-17-hydroxy-2-oxa-5-androstan-3-one (both racemic mixtures andoptically active enantiomers) as well as pharmaceutically acceptableesters thereof. For example, an oxandrolone product which iscommercially available is the Oxandrin* tablet from BTG PharmaceuticalsCorp., Iselin, N.J. 08830, which is17α-methyl-17β-hydroxy-2-oxa-5α-androstan-3-one. This product was usedthroughout the studies described herein.

Protein supplement as used herein encompasses any nutritionallyeffective protein supplement including commercially available proteinsupplements.

Protein supplement Met-Rx contains 74 gram/liter protein, 48 gram/litercarbohydrate and 8 gram/liter fat.

A wound as used herein is a breach in the continuity of skin tissue.Examples of wounds are punctures, incisions, excisions, lacerations,abrasions, ulcers and burns. Examples of ulcers as used herein areulceration of the heel in a diabetic patient and decubitus ulcers inbedridden patients.

A skin graft as used herein encompasses an autograft or an allograft.

Oxandrolone may be administered orally, intravenously, intramuscularly,subcutaneously, topically, intratracheally, intrathecally,intraperitoneally, rectally, vaginally or intrapleurally.

If oxandrolone is administered orally, it is administered in the form ofa tablet, a pill, a liquid or a capsule.

A liquid may be administered in the form of a solution or a suspension.

The compositions produced in accordance with the invention may compriseconventional pharmaceutically acceptable diluents or carriers. Tablets,pills, liquids and capsules may include conventional excipients such aslactose, starch, cellulose derivatives, hydroxypropyl methylcelluloseand magnesium stearate. Suppositories may include excipients such aswaxes and glycerol. Injectable solutions will comprise sterilepyrogen-free media such as saline and may include buffering agents,stabilizing agents, solubilizing agents or preservatives. Conventionalenteric coatings may also be used.

Compositions for topical administration may be in the form of creams,ointments, lotions, solutions, transdermal delivery systems, transdermalpatches or gels.

The subject invention provides a method of treating burn-induced weightloss in a burn patient which comprises administering a therapeuticallyeffective amount of an oxandrolone to the patient.

The subject invention further provides a method of treating burn-inducedweight loss in a burn patient which comprises administering atherapeutically effective amount of an oxandrolone in conjunction with aprotein supplement to the patient.

The subject invention provides a use of an oxandrolone in thepreparation of a composition to treat burn-induced weight loss in a burnpatient. This composition may optionally comprise a protein supplement.

In a preferred embodiment, the amount of oxandrolone is about 1-100 mgper day.

In especially preferred embodiments, the amount of oxandrolone is about20 mg per day or about 80 mg per day.

The oxandrolone may be administered in a solid dosage form, in a liquiddosage form, in a sustained-release formulation or in a once a dayformulation. The liquid dosage form may inter alia be alcohol-based orformulated with a cyclodextrin such as hydroxypropyl-β-cyclodextrin.

The invention further provides a method of treating a wound in a patientsuffering from a wound which comprises administering a therapeuticallyeffective amount of an oxandrolone to the patient.

The subject invention provides a method of improving the rate of healingof a wound in a patient suffering from a wound which comprisesadministering a therapeutically effective amount of an oxandrolone tothe patient.

The subject invention further provides a use of an oxandrolone in thepreparation of a composition to treat a wound in a patient sufferingfrom a wound.

The subject invention also provides a use of an oxandrolone in thepreparation of a composition to improve the rate of healing of a wound.

The subject invention also describes the use of oxandrolone in themaintenance and restoration of lean body mass in burn and traumapatients.

The wound may be a burn wound, an ulcer especially a decubitus ulcer(pressure sore), a skin graft or any form of wound including a traumaticwound.

Oxandrolone may be administered in conjunction with glutamine or humangrowth hormone.

The subject invention further provides a composition for use in topicaltreatment of wounds comprising an oxandrolone and a pharmaceuticallyacceptable carrier.

Such topical composition may be used for the treatment of woundsincluding burns and ulcers especially decubitus ulcers (pressure sores).

EXAMPLES

The Examples which follow are set forth to aid in understanding theinvention but are not intended to, and should not be construed to, limitits scope in any way.

Example 1 The effect of oxandrolone on post-burn catabolism (I)

A study on the effect of oxandrolone on post-burn patients was performedas described below.

Patient characteristics

Patients included in the study had a deep burn of 30-50% of bodysurface. The patients included in this study had undergone:

a. catabolic phase until 80-90% of wound closure (4-10 weeks);

b. loss of 15-25% body weight (mostly lean body mass) during catabolicphase despite optimum nutrition;

The recovery of anabolic phase usually last 8-16 weeks with peakanabolism in the first 8 weeks.

The transition from “catabolic” to recovery “anabolic” was defined by:

a. No need for life support measures, being stable and out of theIntensive Care Unit (ICU);

b. No active infection (stress);

c. Open wound (not counting donor sites) not exceeding 10% Total BodySurface (TBS);

d. Patient taking oral diet with supplements or tube feeding (offparenteral feeding);

e. patient can actively participate in a physical therapy program withactive ROM exercises accentuating the anabolic stimulus of exercise.

All patients were located in the burn step-down unit or in an acuterehabilitation hospital where daily information is retrieved from thephysiatrist, nutritionist, and therapist.

The patients were divided into three groups in a prospective randomizedmanner:

Group 1: Standard nutritional goals as defined by the nutrition supportservice.

Group 2: Same as Group 1 plus 2-3 Met-Rx™ (protein supplement) per day(sufficient protein to increase daily protein intake to 2-2.2 g/kg/day).

Group 3: Same as Group 2 plus oxandrolone 20 mg orally four times daily.

Measurements

The following factors were checked:

a. Subjective energy level (per Braintree study) 0-10;

b. Physical therapy index¹ (per Braintree study) 0-10:

-   -   0 completes 25% session with fatigue    -   2 completes 50% session with fatigue    -   4 completes 75% session with fatigue    -   6 completes 100% session with fatigue    -   8 completes 100% session with no fatigue    -   10 completes 100% session and more with no fatigue; assessment        of muscle strength and endurance

c. Weekly weight gain;

d. Daily nutritional profiles;

e. Measurement of lean body mass by bioelective impedance.

The onset of the study was defined as the onset of the recovery phase(anabolic phase). Patients were studied for 3 weeks (from the onset ofanabolism).

Results

The results are shown in FIGS. 1-6 and are described below:

1. The response to the catabolic phase was an 18% body weight lossdespite optimum nutrition. The predicted amount of muscle loss is 70% oftotal loss since 4 lbs muscle are lost for 1 lb of fat.

2. The subjective energy level at the end of catabolism was 1-2 asexpected.

3. Calorie and protein intake:

-   -   Group I (10 patients): Despite high calorie, high protein diets        and supplements or tube feedings, the calorie intake was below        25 cal/kg and protein intake below 1.5 g/kg protein. Patients        were generally anorexic, felt full and did not like the        supplements. Energy level and therapy index remained low for        three weeks.

Group II (7 patients): All patients liked the Met-Rx™ and actually atebetter overall. Non-protein caloric intake improved slightly butsignificantly while protein intake doubled. Subjective energy level andquality of therapy were markedly increased and weight gain was doublethat of Group I unaccountable by the modest increase in calories alone.

Group III (4 patients): Nutritional profile was comparable to Group IIwith an apparent added stimulus to food intake. Weight gain was fourtimes that of Group I and energy level and therapy markedly improved.

Thus, increased protein intake in the form of Met-Rx™ markedly improvedthe rate of functional return in the recovery period. Attempt atimproving nutrition with other standard nutrients was unsuccessful. Thecombination of Met-Rx™ and oxandrolone results in a great weight gainconsidered to be 80% lean body weight gain by bioelective impedancemeasurements.

Example 2 The effect of oxandrolone on post-burn catabolism (II)

Another study on the effect of oxandrolone on post-burn patients wascarried out as follows.

Patient Characteristics

Patients included in the study had a deep burn of 30-50% of bodysurface, reached recovery phase in about 4-6 weeks post-burn andrequired hospitalization for at least 3 weeks during the recovery phase.

The onset of the study was defined as the onset of the recovery phase(anabolic phase). The study period included the first three weeks of therecovery phase. Although somewhat arbitrary, the beginning of therecovery period was determined for all patients using the followingcriteria:

a. No need for life support measures, with a stable cardiopulmonarystatus;

b. No active infection;

c. Basal body temperature below 99.5° F.;

d. Metabolic rate at rest (indirect calorimetry) being less than 130% ofnormal;

e. Open wound (not counting donor sites) not exceeding 10% PBS;

f. Patient taking adequate oral diet with supplements or tube feedingand off all parenteral feeding;

g. active participation in a physical therapy program includingresistance exercises especially to large muscle groups.

The patients were divided into three groups in a prospective randomizedmanner:

Group 1: High protein high calorie ad lib oral diet and proteinsupplement Met-Rx™. The supplement was given in a quantity equal toapproximately one liter so that total protein intake would approximate 2g/kg/day.

Group 2: Same as Group I with the addition of oxandrolone 10 mg orallytwice a day.

Group 3: ad lib oral diet and a protein hydrolysate supplement(Ensure-HN or Sustacal). These supplements contain approximately 40-45g/l protein, 140-150 g/l carbohydrate and 30-37 g/l fat. Daily proteinintake consumed equalled 1.3-1.5 g/kg or 75% above the RDA value forhealthy normals of 0.8 g/kg. This group was managed in the ten monthsprior to the onset of this study.

All patients were located in the burn/trauma step-down unit and thentransferred to an acute rehabilitation hospital usually within the firstweek of onset of the recovery period. A burn nurse coordinator followedall patients at the rehabilitation hospitals. All patients weremonitored until discharge but only the first three week period was usedfor the study period.

Measurements

The following factors were checked:

a. Fatigue was measured objectively through increases in pulse of over75% of predicted maximum (based on age) and a respiratory rate exceeding30 breaths per minute beyond one minute after completion of theactivity.

b. Muscle function was quantitated using a physical therapy index. Thephysical therapy program was determined for each patient by the burntherapist team based on optimum projected goals to be achieved at thethree week period. Standard isokinetic and resistance exercises wereused to increase strength. Ambulation, stair climbing and the stationarybike were used to increase endurance. Since the basic components oftherapy programs were nearly identical between patients, an index wasdeveloped which quantitated progress of patient performance:

-   -   0 completes 25% session with fatigue    -   2 completes 50% session with fatigue    -   4 completes 75% session with fatigue    -   6 completes 100% session with fatigue    -   8 completes 100% session with no fatigue    -   10 completes 100% session and more with no fatigue;

c. Body weight;

d. Daily nutritional profiles;

e. Liver function

Within each group, paired data was analyzed using Dunnett's T-testcomparing individual time periods. Between groups, analysis was comparedby use of a nonparametric method, the Wilcoxan Signed Rank Test.Standard regression analysis was also performed. A p<0.05 was consideredsignificant.

Results

The results are shown in FIGS. 7-9 and are described below:

All patients survived and have since been discharged to home. Groups 1and 2 were evenly matched as to age, size of injury, period in thecatabolic phase and weight loss. Group 1 had six patients, four malesand two females. Group 2 had seven patients, four males and threefemales. Three patients in each group had a significant inhalationinjury requiring initial ventilatory support in excess of two weeks.Weight loss in these patients did not exceed that for the group as awhole. Weight loss averaged 10-12% of reported pre-burn weight in bothGroup 1 and 2. An unknown portion of the weight loss was likely due toloss of tissue from wound excision as all patients had at least fourexcisions and graftings, 50% of procedures being excisions to fascia.once the transition to the recovery phase was defined, no patientdeveloped a significant infection or other acute process which wouldre-initiate the stress response.

Nutritional Profile

Mean data±standard deviation is shown in FIG. 7. Caloric intake wasalmost identical between all groups. Compliance with the supplement(MET-Rx) was >90% as the product flavor and texture could be adjusteddepending on patient preference. Protein intake was identical in bothGroups 1and 2 being 2.0-2.2 g/kg/day as designed, compared toretrospective Group 3 who were given a high calorie, protein diet withstandard supplements with a protein content which equalled 1.3-1.4 g/kg.

Liver Function Teats

One patient in both groups had a transient increase in alkalinephosphatase which resolved spontaneously.

Weight Gain

There was 2.5 to 3 pound weight gain in Group 1 per week, consistentlyover the three week study period (FIG. 8). In Group 2 weight gain overthe three week period was double that of Group 1, a statisticallysignificant difference. Weight gain was significantly increased in bothGroups 1 and 2 over the retrospective Group 3.

Physical Therapy Index

In Group 1, the therapy index, a measure of muscle strength andendurance, increased rapidly and most patients were able to compete theentire expected program by the three week period without fatigue (FIG.9). In Group 2, performance exceeded expectations, especially by weekthree. Expectations were in large part based on the standard gains insevere burns of this size in the early recovery phase previouslymanaged. Both Groups 1 and 2 showed a significant increase in functionover Group 3 at weeks two and three with Group 2 being significantlyhigher than either of the other groups.

Discharge Time

Average time of discharge from the rehabilitation or recovery phase tohome for Group 1 was 26±5 days and Group 2 was 22±4 days while in Group3 length of stay was 35±7 days. The average patient length of stay inthe burn center was 25 days indicating the rapid wound closure andtransfer to the rehabilitation center.

SUMMARY

A doubling of weight gain was noted in Group 1 using the proteinhydrolysate MET-Rx for the same calorie intake compared to retrospectiveGroup 3 and a marked improvement in muscle function. The biologic valueof the added protein is reported to be greater than 95% by themanufacturer (MET-Rx, US, Inc., Irvine, Calif.). This value indicatesthe percent of nitrogen in the hydrolysate retained by the body. Mostavailable supplements use casein as the major protein. Casein has abiologic value of 60-70%. The addition of approximately 74 more grams ofprotein a day would not explain this doubling of weight unless all theadded protein was used for muscle synthesis, a response only expectedwith an added anabolic stimulus. However, recent data on proteinhydrolysate would indicate that biologic properties of a proteinhydrolysate exceed that of the contained nitrogen and that bioactivepeptides produced by hydrolysis are absorbed intact and can increaseanabolism and wound healing. Most of these peptides remainuncharacterized. If all the protein were converted to fat, this wouldresult in only one half a pound of weight gain a week. Therefore, mostof the 2.5 pound weight gain would need to be fat free or lean tissue.Correlation with increased strength also indicates the weight to bemostly muscle.

The addition of oxandrolone to the increased protein intake resulted ina marked increase in weight nearly four times that of retrospectiveGroup 3 which at the time were ideally nutritionally managed. Rate ofrestoration of muscle function was also significantly increased in theoxandrolone group over protein alone. This rate of weight gain is likelymuscle mass as opposed to fat since non-protein calorie intake was thesame for both Groups 1 and 3. In addition, strength increased anddischarge time decreased although the latter may not be a sensitiveindication. Anabolic agents are known to markedly increase theefficiency of protein synthesis especially in muscle. Since one pound ofmuscle is 100 grams of protein and the rest is water, muscle weightgains can occur rapidly when the efficiency of anabolism is accentuated.Weight gain due to water retention is feasible, however water retentionis not reported to occur with oxandrolone in doses below 80 mg.

In addition, 3 of 6 patients were followed for eight weeks afterdiscontinuation of three weeks of oxandrolone and the weight remained.No hirsutism has been seen in the three women in the group and atransient small increase in alkaline phosphatase in one patient was theonly chemical abnormality noted. This patient also had gallstones andthe role of oxandrolone is questionable. Since the gain of muscle overand above normal body composition by body builders using anabolic agentsdiminishes with discontinuation of the drug the finding of maintenanceof weight is important.

In summary, the rate of weight gain and muscle function can besignificantly increased in the recovery phase after major burn using theanabolic steroid oxandrolone in combination with a high protein intakeincluding a protein hydrolysate. This data indicates that manipulationof the recovery phase to shorten disability time is very feasible andthat endogenous anabolic activity can be markedly increased.

Example 3 Oxandrolone treatment of patients suffering from pressuresores.

A paraplegic patient was suffering from pressure sores (decubitusulcers) which had been unhealed for over one year. This patient wastreated with oxandrolone (20 mg per day orally) and the sores began toheal. This preliminary result demonstrates that oxandrolone treatmentpromoted wound healing in decubitus ulcers of long duration. Furtherexperiments using oxandrolone for treatment of pressure sores and otherwounds are planned.

REFERENCES

1. Herndon et al., Treatment of Burns, Curr. Probl. Surg., 1987, Volume2, pp. 347-373.

2. Wolfe R. R., Nutrition and metabolism in burns, In Chernow B. andShoemaker W. C., eds., Critical Care, State of the Art, Fullerton,Calif., Society of Critical Care Medicine, 1986, Volume 7, pp. 19-61.

3. Ziegler T., In New Horizons-Frontiers in Critical Care Nutrition,SMMC Fullerton Calif., 1994, p. 244-256.

4. Fox et al. (1962), J. Clin. Endocrinol. Metab. 22: 921-924.

5. Karim et al. (1973), Clin. Pharmacol. Therap. 14: 862-869.

6. Masse et al. (1989), Biomedical and Environmental Mass Spectrometry18:429-438.

7. Mendenhall et al. (1993), Hematology 17(4): 564-576.

8. Bonkovsky et al. (1991), The American Journal of Gastroenterology86(9): 1209-1218.

1-29. (canceled)
 30. A method of restoring lean body mass in a patientafflicted with catabolism induced weight loss which comprisesadministering to the patient 10 mg to 100 mg of oxandrolone per day inconjugate with a protein supplement, so as to thereby restore lean bodymass in the patient.
 31. The method of claim 30, wherein the amount ofoxandrolone administered is about 80 mg per day.
 32. The method of claim30, wherein the amount of oxandrolone administered is about 20 mg perday.
 33. The method of claim 30, wherein the amount of oxandroloneadministered is about 10 mg per day.
 34. The method of claim 30, whereinthe oxandrolone is administered orally, topically, or by injection. 35.The method of claim 30, wherein the oxandrolone is in a solid dosageform, a liquid dosage form, or a sustained-release formulation.
 36. Themethod of claim 30, wherein the oxandrolone is17α-methyl-17β-hydroxy-2-oxa-5α-androstan-3-one.
 37. The method of claim30, wherein a daily protein intake of approximate 2.0 g/kg/day isachieved in the patient.
 38. The method of claim 30, wherein theoxandrolone is administered for a period of three weeks.